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901.
902.
903.
The coupling between the mechanical properties of enzymes and their biological activity is a well-established feature that has been the object of numerous experimental and theoretical works. In particular, recent experiments show that enzymatic function can be modulated anisotropically by mechanical stress. We study such phenomena using a method for investigating local flexibility on the residue scale that combines a reduced protein representation with Brownian dynamics simulations. We performed calculations on the enzyme guanylate kinase to study its mechanical response when submitted to anisotropic deformations. The resulting modifications of the protein's rigidity profile can be related to the changes in substrate binding affinity observed experimentally. Further analysis of the principal components of motion of the trajectories shows how the application of a mechanical constraint on the protein can disrupt its dynamics, thus leading to a decrease of the enzyme's catalytic rate. Eventually, a systematic probe of the protein surface led to the prediction of potential hotspots where the application of an external constraint would produce a large functional response both from the mechanical and dynamical points of view. Such enzyme-engineering approaches open the possibility to tune catalytic function by varying selected external forces. 相似文献
904.
Transmissible spongiform encephalopathies, or prion diseases, are caused by misfolding and aggregation of the prion protein PrP. Conversion from the normal cellular form (PrPC) or recombinant PrP (recPrP) to a misfolded form is pH-sensitive, in that misfolding and aggregation occur more readily at lower pH. To gain more insight into the influence of pH on the dynamics of PrP and its potential to misfold, we performed extensive molecular-dynamics simulations of the recombinant PrP protein (residues 90-230) in water at three different pH regimes: neutral (or cytoplasmic) pH (∼7.4), middle (or endosomal) pH (∼5), and low pH (<4). We present five different simulations of 50 ns each for each pH regime, amounting to a total of 750 ns of simulation time. A detailed analysis and comparison with experiment validate the simulations and lead to new insights into the mechanism of pH-induced misfolding. The mobility of the globular domain increases with decreasing pH, through displacement of the first helix and instability of the hydrophobic core. At middle pH, conversion to a misfolded (PrPSc-like) conformation is observed. The observed changes in conformation and stability are consistent with experimental data and thus provide a molecular basis for the initial steps in the misfolding process. 相似文献
905.
906.
Familial hypocholesterolemia, namely abetalipoproteinemia, hypobetalipoproteinemia and chylomicron retention disease (CRD), are rare genetic diseases that cause malnutrition, failure to thrive, growth failure and vitamin E deficiency, as well as other complications. Recently, the gene implicated in CRD was identified. The diagnosis is often delayed because symptoms are nonspecific. Treatment and follow-up remain poorly defined. The aim of this paper is to provide guidelines for the diagnosis, treatment and follow-up of children with CRD based on a literature overview and two pediatric centers 'experience. The diagnosis is based on a history of chronic diarrhea with fat malabsorption and abnormal lipid profile. Upper endoscopy and histology reveal fat-laden enterocytes whereas vitamin E deficiency is invariably present. Creatine kinase (CK) is usually elevated and hepatic steatosis is common. Genotyping identifies the Sar1b gene mutation. Treatment should be aimed at preventing potential complications. Vomiting, diarrhea and abdominal distension improve on a low-long chain fat diet. Failure to thrive is one of the most common initial clinical findings. Neurological and ophthalmologic complications in CRD are less severe than in other types of familial hypocholesterolemia. However, the vitamin E deficiency status plays a pivotal role in preventing neurological complications. Essential fatty acid (EFA) deficiency is especially severe early in life. Recently, increased CK levels and cardiomyopathy have been described in addition to muscular manifestations. Poor mineralization and delayed bone maturation do occur. A moderate degree of macrovesicular steatosis is common, but no cases of steatohepatitis cirrhosis. Besides a low-long chain fat diet made up uniquely of polyunsaturated fatty acids, treatment includes fat-soluble vitamin supplements and large amounts of vitamin E. Despite fat malabsorption and the absence of postprandial chylomicrons, the oral route can prevent neurological complications even though serum levels of vitamin E remain chronically low. Dietary counseling is needed not only to monitor fat intake and improve symptoms, but also to maintain sufficient caloric and EFA intake. Despite a better understanding of the pathogenesis of CRD, the diagnosis and management of the disease remain a challenge for clinicians. The clinical guidelines proposed will helpfully lead to an earlier diagnosis and the prevention of complications. 相似文献
907.
A study on the applicability of implantable microchip transponders for body temperature measurements in pigs 总被引:1,自引:0,他引:1
Background
The applicability of an electronic monitoring system using microchip transponders for measurement of body temperatures was tested in 6-week-old conventional Danish weaners infected with classical swine fever virus (CSFV). Subcutaneous tissue temperatures obtained by the implantable transponders were compared with rectal temperatures, recorded by a conventional digital thermometer. 相似文献908.
Fossil wood collections at the Natural History Museum, London, were searched for the type material of two important species, described as early as 1831 by Witham, on the basis of material at least partly furnished by Nicol and collected in the Liassic of Whitby (Yorkshire, UK). The names given to these two species by Witham are the basionyms for more than ten other species names, while these species names also provide syntypes for several generic names. Despite this, the original material has been only rarely and partly revised, leading to much confusion.We managed to locate some of the original material. Several topotypes were also studied. On the basis of this review we propose here a neotypification for Peuce huttoniana Witham, a lectotypification for Cupressinoxylon barberi Seward and a lectotypification for Tiloxylon Hartig. We evidence several taxonomical and nomenclatural synonymies, assign Peuce lindleyana Witham to Protocedroxylon and P. huttoniana to Xenoxylon Gothan, and introduce the new combination Xenoxylon huttonianum (Witham) nov. comb. as the correct name for Xenoxylon ellipticum Gottwald & Holleis ex Schultze-Motel.A topotype of Araucariopitys americana Hollick & Jeffrey was also reviewed, which, together with previous results, leads us to suggest that Araucariopitys Hollick & Jeffrey, Protocedroxylon Gothan and Planoxylon Stopes should not be considered as taxonomical synonyms. This point is crucial to the interpretation of the fossil record of Early Abietinae. 相似文献
909.
910.
Zornitza Andreeva Deborah Barton William J. Armour Min Y. Li Li-Fen Liao Heather L. McKellar Kylie A. Pethybridge Jan Marc 《Planta》2010,232(5):1263-1279
The phospholipase protein superfamily plays an important role in hormonal signalling and cellular responses to environmental
stimuli. There is also growing evidence for interactions between phospholipases and the cytoskeleton. In this report we used
a pharmacological approach to investigate whether inhibiting a member of the phospholipase superfamily, phospholipase C (PLC),
affects microtubules and actin microfilaments as well as root growth and morphology of Arabidopsis thaliana seedlings. Inhibiting PLC activity using the aminosteroid U73122 significantly inhibited root elongation and disrupted root
morphology in a concentration-dependent manner, with the response being saturated at 5 μM, whereas the inactive analogue U73343
was ineffective. The primary root appeared to lose growth directionality accompanied by root waving and formation of curls.
Immunolabelling of roots exposed to increasingly higher U73122 concentrations revealed that the normal transverse arrays of
cortical microtubules in the elongation zone became progressively more disorganized or depolymerized, with the disorganization
appearing within 1 h of incubation. Likewise, actin microfilament arrays also were disrupted. Inhibiting PLC using an alternative
inhibitor, neomycin, caused similar disruptions to both cytoskeletal organization and root morphology. In seedlings gravistimulated
by rotating the culture plates by 90°, both U73122 and neomycin disrupted the normal gravitropic growth of roots and etiolated
hypocotyls. The effects of PLC inhibitors are therefore consistent with the notion that, as with phospholipases A and D, PLC
likewise interacts with the cytoskeleton, alters growth morphology, and is involved in gravitropism. 相似文献